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Chapter 6
Synthesis of benzodiazepines
6.1 Introduction
The clinical importance and commercial success associated with the 1,4-
benzodiazepine class of central nervous system (CNS)-active agents and the utility of
1,4-diazepines as peptide mimetic scaffolds have led to their recognition by the
medicinal chemistry community as privileged structures. This ring system has
demonstrated considerable utility in drug design, with derivatives demonstrating a
wide range of biological activities.
The ring numbering and accepted system of nomenclature for 1,4-diazepines
are illustrated in the structures (Figure-1). These structures are representatives of the
tautomeric forms that have been most studied. Examples of all the fully unsaturated
monocyclic 1,4-diazepines have been described and all are very unstable. In the
dihydro-1,4-diazepines, the 2,3-dihydro-1H compounds have been studied most. For
benzo-analogues the 3H series are usually more stable than 1H and although the
parent compounds of both series are unknown, there is an extensive chemistry on
substituted analogous especially in 3H series. The benzodiazepine-2-ones have been
widely studied as benefits their commercial importance.
Figure-1
On the other hand, examples of the serendipitous discovery of new drugs
based on an almost random screening of chemicals synthesized in the laboratory are
striking. Since 1960, when chlordiazepoxide (Librium) entered in the market, efforts
to discover new biologically active compounds with limited side effects in
benzodiazepines are going on which are reflected by the important number of
publication focused in this subject. 1-5
Department of Chemistry, Saurashtra University, Rajkot-360005 201